entry inhibitors

WordNet

1. a written record of a commercial transaction (同)accounting entry, ledger entry
2. an item inserted in a written record
3. a substance that retards or stops an activity

PrepTutorEJDIC

1. 〈C〉〈U〉(場所などに)『入ること』,『入場』,登場;(団体・競技などへの)参加,加入(entrance)《+『into』+『名』》 / 〈C〉《おもに米》(‥への)入り口(entrance),玄関《+『of』(『to』)+『名』》 / 〈C〉(帳簿・日記・表などの)『記載事項』,項目;(…の)『記入』《+『of』+『名』》 / 〈C〉(競技・コンテストなどの)『参加者』,参加作品《+『for』(『in』)+『名』》 / 〈C〉(辞書などの)見出し語
2. 抑制する人(物) / 化学反応抑制剤

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/16 17:38:21」(JST)

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[Wiki en表示]

For an entry-level drug, see Gateway drug theory.

Entry inhibitors, also known as fusion inhibitors, are a class of antiretroviral drugs, used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell. By blocking this step in HIV's replication cycle, such agents slow the progression from HIV infection to AIDS.

An HIV virion binds to a CD4+ human cell. The two bottom pictures depict two proposed models of HIV fusion with the cell.

HIV entry

Proteins

There are several key proteins involved in the HIV entry process.

• CD4, a protein receptor found on the surface of helper T cells in the human immune system, also called CD4+ T cells
• gp120, a protein on HIV surface that binds to the CD4 receptor
• CCR5, a second receptor found on the surface of CD4+ cells and macrophages, called a chemokine co-receptor
• CXCR4, another chemokine co-receptor found on CD4+ cells
• gp41, a HIV protein, closely associated with gp120, that penetrates the cell membrane

Binding, fusion, entry sequence

HIV entry into a human cells requires the following steps in sequence.

1. The binding of HIV surface protein gp120 to the CD4 receptor
2. A conformational change in gp120, which both increases its affinity for a coreceptor and exposes gp41
3. The binding of gp120 to a coreceptor either CCR5 or CXCR4
4. The penetration of the cell membrane by gp41, which approximates the membrane of HIV and the T cell and promotes their fusion
5. The entry of the viral core into the cell

Entry inhibitors work by interfering with one aspect of this process.

Approved agents

• Maraviroc (Celsentri) binds to CCR5, preventing an interaction with gp120. It is also referred to as a "chemokine receptor antagonist" or a "CCR5 inhibitor."
• Enfuvirtide (Fuzeon) binds to gp41 and interferes with its ability to approximate the two membranes. It is also referred to as a "fusion inhibitor."

Investigation / experimental agents

Other agents are under investigation for their ability to interact with the proteins involved in HIV entry and the possibility that they may serve as entry inhibitors.

• TNX-355, a monoclonal antibody that binds CD4 and inhibits the binding of gp120
• PRO 140, a monoclonal antibody that binds CCR5
• BMS-488043, a small molecule that interferes with the interaction of CD4 and gp120
• Plerixafor was being developed to interfere with interaction between HIV and CXCR4, but showed little useful antiviral activity in recent trials.
• Epigallocatechin gallate, a substance found in green tea, appears to interact with gp120 as do several other theaflavins.
• Vicriviroc, similar to maraviroc, is currently undergoing clinical trials for FDA approval.
• Aplaviroc, an agent similar to maraviroc and vicriroc. Clinical trials were halted in 2005 over concerns about the drug's safety.
• b12 is an antibody against HIV found in some long-term nonprogressors. It has been found to bind to gp120 at the exact region, or epitope, where gp120 binds to CD4. b12 seems to serve as a natural entry inhibitor in some individuals. It is hoped that further study of b12 may lead to an effective HIV vaccine.
• Griffithsin, a substance derived from algae, appears to have entry inhibitor properties.
• DCM205, is a small molecule based on L-chicoric acid, an integrase inhibitor. DCM205 has been reported to inactivate HIV-1 particles directly in vitro and is thought to act primarily as an entry inhibitor.
• CD4 specific Designed Ankyrin Repeat Proteins (DARPins) potently block viral entry of diverse strains and are being developed and studied as potential microbicide candidates

References

External links

• Fusion Inhibitor Resource Center
• HIV+Fusion+Inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

• sp2 -Iminosugar α-glucosidase inhibitor 1-C-octyl-2-oxa-3-oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1-integrin, and FAK signaling pathways.

• Gueder N1, Allan G1, Telliez MS1, Hague F1, Fernandez JM2, Sanchez-Fernandez EM3, Ortiz-Mellet C3, Ahidouch A1,4, Ouadid-Ahidouch H1.
• Journal of cellular physiology.J Cell Physiol.2017 Dec;232(12):3631-3640. doi: 10.1002/jcp.25832. Epub 2017 Apr 25.
• PMID 28145580

• "Fusion and binding inhibition" key target for HIV-1 treatment and pre-exposure prophylaxis: targets, drug delivery and nanotechnology approaches.

• Malik T1, Chauhan G1,2, Rath G1, Murthy RS1, Goyal AK1.
• Drug delivery.Drug Deliv.2017 Nov;24(1):608-621. doi: 10.1080/10717544.2016.1228717.
• PMID 28240046

• Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib and ribociclib.

• Costa R1, Costa RB2, Talamantes SM3, Helenowski I4, Peterson J5, Kaplan J2, Carneiro BA2, Giles FJ2, Gradishar WJ2.
• Breast (Edinburgh, Scotland).Breast.2017 Oct;35:1-7. doi: 10.1016/j.breast.2017.05.016. Epub 2017 Jun 12.
• PMID 28618307

Japanese Journal

• Characterization of the glycoproteins of bat-derived influenza viruses

• Virology 488, 43-50, 2016-01-15
• NAID 120005906991

• Anti-Hepatitis C Virus Activity of a Crude Extract from Longan (Dimocarpus longan Lour.) Leaves

• Japanese Journal of Infectious Diseases 69(3), 213-220, 2016
• NAID 130005152001

• Assessment of flavaglines as potential chikungunya virus entry inhibitors

• Microbiology and immunology 59(3), 129-141, 2015-03
• NAID 40020416281

Related Links

• Entry Inhibitors

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information! Entry inhibitors are ...

• Entry Inhibitors (including Fusion Inhibitors)

What are Entry Inhibitors (including Fusion Inhibitors)? Entry inhibitors work by preventing HIV from entering healthy CD4 cells (T-cells) in the body. They work differently than many of the approved anti-HIV drugs—the protease inhibitors (PIs), the nucleoside reverse transcriptase inhibitors (NRTIs), and the ...

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★リンクテーブル★

関連記事	「entry」「inhibitor」

「entry」

　　[★]

• n.

• 移行、侵入、流入、エントリー、入口

関

entrance、immigration、incurrent、inflow、influx、inlet、intrude、intrusion、invade、invasion、invasive、penetrate、penetration、shift、transfer、transit、transition、transitional、translocation、travel

　 　 　

「inhibitor」

　　[★]

• n.

• 阻害剤、阻害薬、抑制薬、抑制剤、(内在性物質について)インヒビター、抑制物質

関

blocker、depressant、suppressant